One underserved group is the 4 million homeless persons in the US among whom cigarette smoking rate is an alarming 70% or more;these rates are 3 times higher than national average. Two of the three leading causes of death among homeless persons, heart disease and cancer are tobacco related. Despite very high smoking prevalence and disease burden in this population smoking cessation research have not been extended to the homeless. Recent studies including data from our research team show a considerable degree of readiness to quit smoking by homeless smokers and that nicotine replacement therapy plus counseling show promise. However, homeless persons face many challenges that may constitute barriers for them to adhere to smoking cessation treatments even if such treatments have been proven effective in the general population. In order to reduce smoking-related health disparities within this underserved population, it is critical that cessation interventions including strategies to improve treatment adherence be developed to include homeless smokers. The primary aim of this study is to assess the effects of adherence-focused motivational interviewing to help homeless persons quit smoking.This community-based randomized study will recruit 428 participants from homeless shelters and facilities in the 7-County greater Minneapolis/St. Paul metro area. The study will have an Intervention and a Comparison arm.Participants in both arms will receive 21 mg nicotine patches for eight weeks. In addition, those in the Intervention arm will receive five adherence- focused Ml sessions while those in the Comparison arm will receive a one-time brief advice to quit smoking. The primary outcome of the study is biochemically-verified 7-day point prevalence abstinence from cigarettes at 6 months. Other outcomes include adherence to nicotine patch and the moderating effects ofsubstance abuse and psychiatric co-morbidities on the efficacy of Ml among homeless smokers. In addition the study employs an innovative protocol for "patch checks" to measure by direct observation adherence to study pharmacotherapy.Recruitment and retention will be enhanced by use of bus passes for transportation, debit cards, attractive intervention materials, collaboration with homeless shelters, and advice from a community advisory board. The study is innovative in a number of ways including, it fills a critical gap in smoking research by extending smoking cessation research to a poor and underserved population using evidence- based approaches pharmacotherapy and motivational interviewing counseling;it evaluates a counseling approach that allows participants to address multiple challenges that could impact smoking andtreatment adherence;and we expect that findings from the proposed study would serve as impetus to establish .Aubest practices.Au for evidence-based smoking cessation interventions for homeless populations and to provide a model for how to overcome barriers to cancer prevention services.